Human Herpesvirus 6 Infection as a Trigger of Multiple Sclerosis

Voumvourakis, Konstantine I.; Kitsos, Dimitrios; Tsiodras, Sotirios; Petrikkos, George; Stamboulis, Eleftherios

doi:10.4065/mcp.2010.0350

Cited by 42 publications

(32 citation statements)

References 80 publications

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“…The role of HHV-6 as a potential trigger of white matter demyelination has generated considerable research interest in the recent years [10,11]. The association between HHV-6 and multiple sclerosis, the most common demyelinating disease of human central nervous system (CNS), was reviewed by Voumvourakis and colleagues [12]. Some other studies suggest that HHV-6 may play a role in the pathogenesis of another demyelinating disorder–progressive multifocal leukoencephalopathy [13].…”

Section: Introductionmentioning

confidence: 99%

Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection

Skuja¹,

Zieda²,

Rāviņa³

et al. 2017

PLoS ONE

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Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them.

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Section: Introductionmentioning

confidence: 99%

Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection

Skuja¹,

Zieda²,

Rāviņa³

et al. 2017

PLoS ONE

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“…Possible etiological factors of multiple sclerosis may include herpes virus infections, especially HHV-6 [38,39]. …”

Section: Discussionmentioning

confidence: 99%

Clinical Manifestation of Self-Limiting Acute Retinal Necrosis

et al. 2014

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BackgroundThe purpose of this paper was to present a case series of self-limiting, peripheral acute retinal necrosis and to demonstrate efficacy of treatment with valacyclovir in patients resistant to acyclovir. The diagnosis was made on ophthalmoscopic examination and positive serum tests for herpes viruses.Material/MethodsTen patients (6F and 4M) aged 19–55 years were diagnosed and treated for self-limiting acute retinal necrosis (ARN). The following endpoints were reported: visual outcomes, clinical features, disease progression, treatment, and complications. Patients received only symptomatic treatment because they did not consent to vitreous puncture.ResultsPeripheral, mild retinitis was diagnosed in all eyes at baseline. Initially, all patients were treated with systemic acyclovir (800 mg, 5 times a day), prednisone (typically 40–60 mg/day), and aspirin in an outpatient setting. In 6 patients, treatment was discontinued at 6 months due to complete resolution of the inflammatory process. Four patients with immune deficiency showed signs and symptoms of chronic inflammation. Two patients did not respond to acyclovir (2 non-responders); however, those patients were successfully treated with valacyclovir. Complete resolution of inflammatory lesions was observed in 8 patients. In 2 patients, the disease progressed despite treatment – 1 female patient after kidney transplant who stopped the prescribed medications, and 1 male patient with SLE and antiphospholipid syndrome who experienced breakthrough symptoms on-treatment. He died due to cerebral venous sinus thrombosis. Neurological complications (encephalitis and meningitis) were observed in 2 female patients. Prophylactic laser photocoagulation was performed in 1 subject.ConclusionsA series of cases of self-limiting acute retinal necrosis (ARN) is presented. This clinical form of ARN can resemble toxoplasmic retinitis in some cases. Oral antiviral medications provide an effective alternative to intravenous formulations in patients with self-limiting ARN. Retinitis is associated with the risk of encephalitis.

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“…This is especially apparent in the majority of studies that only examine sera and/or CSF or cell free DNA [40–44]. HHV-6 reactivation has been documented in small subsets of patients in several diseases [45]. As noted earlier, most cases of HHV-6 reactivation are benign; even though the virus is present and replicating, patients remain asymptomatic in most cases.…”

Section: Discussionmentioning

confidence: 99%

Monitoring of Active Human Herpes Virus 6 Infection in Iranian Patients with Different Subtypes of Multiple Sclerosis

Ramroodi

Sanadgol

Ganjali

et al. 2013

Journal of Pathogens

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Background. Recently, it has been suggested that human herpes virus 6 (HHV6) may play a role in the pathogenesis of multiple sclerosis (MS). Our purpose is to determine the incidence of reactivated HHV6 in MS patients. Methods. Viral sequence analyzed by qPCR in the peripheral blood mononuclear cells (PBMCs), serum, and saliva samples of different subtypes of MS patients (n = 78) and healthy controls (n = 123). HHV6 IgG and IgM antibody levels measured by ELISA technique in the plasma samples of both groups. Likewise, cerebrospinal fluid (CSF) samples of some MS patients (n = 38) were analyzed for viral sequence. Results. Results demonstrate increased levels of anti-HHV6-IgG (78.2% versus 76.4% in controls; P = NS), and IgM (34.6% versus 6.5% in controls; P < 0.05) in MS patients. Furthermore, RRMS and SPMS patients showed relatively higher anti-HHV6 IgG and IgM compared to PPMS (P < 0.001). Moreover, load of cell-free viral DNA was higher in RRMS and SPMS patients and detected in 60.2% (47/78) of MS patients, compared with 14.6% (18/123) of healthy controls (P < 0.001). Moreover, load of cell-free viral DNA was higher in RRMS and SPMS patients and detected in 60.2% (47/78) of MS patients, compared with 14.6% (18/123) of healthy controls (P < 0.001). Conclusions. The results extend the observation of an increased frequency of systemic reactivated HHV6 infection in MS patients with developed stages of disease.

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Human Herpesvirus 6 Infection as a Trigger of Multiple Sclerosis

Cited by 42 publications

References 80 publications

Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection

Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection

Clinical Manifestation of Self-Limiting Acute Retinal Necrosis

Monitoring of Active Human Herpes Virus 6 Infection in Iranian Patients with Different Subtypes of Multiple Sclerosis

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